The neuromuscular action of certain compounds falling within the series EQU Me.sub.3 N.sup.+ --(CH.sub.2).sub.n --N.sup.+ Me.sub.3
has been reported in the literature. The muscle relaxant activity of two compounds in this series, decamethonium and hexamethonium, is discussed by Paton and Zaimis in Pharmacological Reviews. Vol. 4, (1952), pp 219-253. They observed that decamethonium closely imitated acetylcholine at the neuromuscular junction in certain species tested. By this mechanism of action, decamethonium is classified as a depolarizing type of muscle relaxant. This type of activity is sustained for as long as an effective concentration of the therapeutic agent remains at the receptor site.
Paton and Zaimis further observed that, as the length of the chain between the quaternary nitrogens in decamethonium is shortened, the depolarizing neuromuscular activity was reduced to negligible level. They found that d-tubocurarine acts on post-ganglionic structures and actually antagonizes acetylcholine. It is, therefore, a nondepolarizing muscle relaxant.
There is neither teaching nor suggestion in Paton and Zaimis that a diamine having a polypeptide chain separating quaternary nitrogens would be useful as a muscle relaxant of any type. There is nothing in Paton and Zaimis that would suggest that, were such compounds synthesized, they would have any therapeutic activity.
Thornber et al. NIDA Res. Monograph, 75 (Prog. Opioid Res), 181, (1986) describe the preparation of dimeric pentapeptides by the addition of amino acid moieties to the amino groups of ethylene diamine.
Boger et al., U.S. Patent No. 4,812.442, disclose enzyme tripeptides of the general formula: ##STR2## wherein the designations A,E,G,J and R.sub.1 have a broad variation of meanings. The disclosed peptides can contain only one quaternary amino moiety. They are useful in treating various forms of renin-associated hypertension.
In accordance with the present invention, it has been found that certain peptide amides and amide dimers possess significant nondepolarizing muscle relaxant activity, thus making them useful therapeutically as skeletal muscle relaxants.